Alzheimer’s disease (AD) is an “amyloid-facilitated tauopathy” associated with synaptic dysfunction and neuronal loss causing progressive memory impairments and cognitive dysfunction leading to dementia and death. Currently there is no treatment that slows the progression of AD. However, a recent small trial by Biogen using a human antibody has shown dramatic effects to lower brain amyloid load, and suggested a beneficial clinical effect. Until recently, AD was diagnosed with clinical measures, or by autopsy. However, in the past decade a number of biomarkers including MRI, PET, and cerebrospinal fluid (CSF) markers have been used to characterize the pathology with reasonable sensitivity and specificity.
The goal of ADNI (see adni-info.org) has been to standardize and validate MRI and PET imaging and blood/CSF biomarkers for Alzheimer’s treatment trials. To date we have studied the following groups of subjects: Elders with mild cognitive impairment (MCI) (n= 850); AD (n= 350); Normal Controls (n= 350) and 150 controls with cognitive complaints with: clinical visits, neuropsychological assessments, MRI (structural, perfusion, diffusion-tensor and task-free, resting-state fMRI), FDG PET, amyloid PET (Florbetapir) blood and urine, and CSF (abeta, tau, ptau and other analytes) and whole genome sequencing. The major findings include the observations that many patients diagnosed with dementia due to AD do not have high levels of brain amyloid plaques, suggesting that their dementia is not due to AD pathology. This emphasizes the need for amyloid phenotyping in clinical trials of AD. About 30% of cognitively normal elders (termed “preclinical AD) do have high levels of plaques, and the presence of plaques is a risk factor for cognitive decline. The APOE-4 genotype is associated with greater prevalence of amyloid plaques, and other factors causing greater prevalence of AD. Tau PET imaging is now beginning on a large scale. Similar ADNI-like projects are underway in Australia, Japan, Europe, China, Taiwan, and Korea leading to the “World Wide ADNI network.” and the Parkinson’s Progressive Markers Initiative (PPMI). All ADNI data is available to all scientists in the world, on USC/LONI/ADNI, without embargo. Blood and CSF samples can be requested. ADNI methods are now widely used in clinical treatment trials. Over 900 papers have been published on ADNI data and all scientists are encouraged to explore this rich data set and publish results. The ADNI project already has, and will continue to validate effective diagnostic techniques which can be used for diagnosis and to measure the effects of treatments which slow progression and prevent AD.